This in vitro study investigated the ability of the De Simone Formulation to hydrolyze gliadin peptides associated with Celiac Sprue. The research demonstrated that the De Simone Formulation could completely degrade toxic epitopes, such as the 33-mer peptide, during long-term fermentation of wheat flour. Experiments using intestinal epithelial cells and celiac jejunal biopsies showed that pre-digestion with this formulation significantly reduced intestinal permeability, zonulin release, and the infiltration of CD3+ intraepithelial lymphocytes compared to untreated gliadins. DOI: 10.1016/j.bbadis.2005.09.008

This study examined the capacity of the De Simone Formulation to hydrolyze allergens responsible for wheat allergy. Results showed that while several IgE-binding proteins persisted after standard digestive enzyme treatment, they were completely eliminated after further treatment with the De Simone Formulation. When used as a starter for bread making, the formulation caused a marked degradation of wheat proteins, including alpha-amylase inhibitors. J Food Prot. 2007 Jan;70(1):135-44

This study explored the immunomodulatory effects of the De Simone Formulation on Th2-mediated allergic responses using both in vitro and in vivo mouse models of inhalant allergy. Both live and inactivated versions induced dendritic cell maturation and shifted the cytokine profile toward a Treg/Th0 profile, characterized by increased IL-10 and IFN-gamma production. In vivo, prophylactic intranasal administration significantly reduced allergen-specific IgG1 levels and decreased IL-4 and IL-13 expression while increasing IL-10. DOI: 10.1159/000218116

This research evaluated the therapeutic potential of the De Simone Formulation in a murine model of established food allergy to shrimp tropomyosin. Oral administration significantly reduced clinical anaphylactic symptoms and fecal histamine levels. At the molecular level, treatment suppressed Th2-associated cytokines (IL-4, IL-5, IL-13) and up-regulated regulatory markers, including FOXP3, IL-10, and TGF-beta. DOI: 10.1111/j.1398-9995.2010.02501.x

In a mouse model of peanut allergy, oral supplementation with the De Simone Formulation reduced Th2-mediated inflammation and anaphylactic reactions. This protective effect was mediated by the induction of TGF-beta in the gut mucosa and mesenteric lymph nodes, which promoted the expansion of FOXP3+ and LAP+ regulatory T cells. The findings were confirmed through in vivo blockade of TGF-beta, which abolished the probiotic's protective effects. DOI: 10.1002/mnfr.201300028

This randomized controlled trial investigated whether the De Simone Formulation could alter the fecal microbiota in adult patients with Celiac Disease who remained symptomatic despite a strict gluten-free diet. Participants received 10g daily for 12 weeks. The results showed no statistically significant changes in fecal microbiota counts or blood safety measures between the probiotic and placebo groups. While safe and well-tolerated, the formulation did not significantly alter the measured gastrointestinal microbiota in this specific celiac population at the dose and duration tested. DOI: 10.1155/2016/9048574

In NOD mice, early oral administration of De Simone Formulation markedly reduced diabetes incidence and delayed onset. Protection was associated with reduced insulitis severity, preservation of insulin-positive β-cell area, and increased IL-10 production. The protective effect was transferable by splenocytes and was abrogated by cyclophosphamide, indicating an immune-mediated mechanism. Treatment started later in life had weaker or no durable impact. DOI: 10.1007/s00125-005-1831-2

Using NOD mice, systemic TLR stimulation reduced asthma and delayed diabetes. Oral administration of De Simone Formulation protected NOD mice from both conditions, increasing circulating IL-10 and TGF-β and expanding regulatory T-cell subsets. Protection was associated with reduced destructive insulitis and a shift toward benign peri-insulitis. DOI: 10.1371/journal.pone.0011484

Oral De Simone Formulation prevented and treated high-fat diet-induced obesity and insulin resistance, and improved hyperglycemia in leptin-deficient mice. Treated animals showed reduced body weight, fat mass, hepatic steatosis, and inflammatory cytokines, with increased adiponectin. The formulation altered gut microbiota and elevated colonic butyrate levels. Circulating GLP-1 was markedly increased while ghrelin decreased, consistent with reduced food intake. DOI: 10.1074/jbc.M113.452516

In a 6-week trial of 60 overweight adults, De Simone Formulation alone significantly reduced total cholesterol, triglycerides, LDL, VLDL, and increased HDL, while improving insulin sensitivity and decreasing hsCRP. Fecal microbiota analysis showed increased lactobacilli, bifidobacteria, and streptococci, and reduced E. coli and bacteroides. DOI: 10.1155/2014/348959

In NOD mice, long-term oral De Simone Formulation significantly reduced type 1 diabetes incidence and insulitis severity. Probiotic-treated mice displayed a Lactobacillaceae-enriched microbiota. In the intestine, the formulation decreased IL-1β while upregulating IDO and IL-33, suggesting improved barrier integrity. Intestinal dendritic cells and CX3CR1+ cells were expanded, and Th1/Th17 cells were reduced. DOI: 10.1155/2016/7569431

NOD mice harbor a diabetogenic gut microbiota. Lifelong oral vancomycin or neomycin unexpectedly accelerated diabetes onset with marked dysbiosis and reduced SCFAs. Attempts to correct this with De Simone Formulation failed: the probiotic colonized poorly and did not delay diabetes. The data highlight that early-life antibiotic-driven dysbiosis can potentiate autoimmunity, and that De Simone Formulation alone may be insufficient to overcome a strongly diabetogenic ecosystem. DOI: 10.1038/ismej.2015.114

In an 8-week trial, 72 women with gestational diabetes received De Simone Formulation or placebo. The probiotic group showed significantly lower fasting insulin and HOMA-IR, indicating improved insulin sensitivity. The formulation also significantly reduced IL-6, TNF-α, and hsCRP compared with placebo. No major adverse events were reported. DOI: 10.1155/2016/5190846

In this pilot trial, 17 adolescents with prediabetes received lifestyle counseling plus De Simone Formulation or counseling alone. Recruitment and adherence were challenging with high attrition. At 1 month, fasting glucose was transiently lower in the probiotic group, but by 4 months there were no significant differences. The authors emphasize the need for larger, better-adhered trials. DOI: 10.3390/jcm8101743

Ninety-six children with new-onset type 1 diabetes were randomized to De Simone Formulation or placebo for 3 months. The probiotic group showed significantly greater reduction in HbA1c and larger decreases in insulin dose compared with placebo, while fasting C-peptide levels were preserved. More children in the probiotic arm achieved partial remission. DOI: 10.1111/pedi.13244

In 23 cystic fibrosis patients, De Simone Formulation daily for 4 months significantly altered urinary and fecal metabolite profiles. Principal component analysis showed clear separation of pre- and post-treatment metabolomes. In non-diabetic patients, HOMA-IR showed a small, non-significant decrease. The authors interpret the metabolomic shifts as potentially favorable for glucose metabolism. DOI: 10.1002/ppul.26037

This multicenter, double-blind trial assessed the De Simone Formulation in patients with Crohn's disease after ileocolonic resection. At day 90, severe endoscopic recurrence was not significantly different between groups. However, patients who received the formulation from day 0 showed lower recurrence at day 365 and reduced mucosal cytokine levels. These findings suggest early probiotic administration may help prevent postoperative recurrence and modulate intestinal inflammation. DOI: 10.1016/j.cgh.2014.10.031

A secreted factor from the De Simone Formulation inhibited proteasome activity and reduced colitis severity in mice, suggesting a novel anti-inflammatory mechanism of this probiotic. DOI: 10.1172/JCI28804

In this pilot study, 16 IBD patients with arthralgia received the De Simone Formulation for 8 weeks. Ten reported significant improvement in joint pain without worsening of intestinal symptoms. The probiotic was well tolerated, and no adverse events were observed. These results suggest the De Simone Formulation may be a safe and effective option for IBD-associated arthralgia. DOI: 10.1358/dot.2005.41.7.917341

This study investigated the effects of the De Simone Formulation on intestinal epithelial barrier function using IL-10 gene-deficient mice and human T84 epithelial cells. Daily oral administration for four weeks normalized colonic physiological function and barrier integrity, with significant reduction in TNF-α and IFN-γ. In vitro experiments showed the formulation directly enhanced epithelial resistance and induced tight junction protein expression. DOI: 10.1053/gast.2001.27224

This study explored how the De Simone Formulation exerts anti-inflammatory effects in DSS-induced and TNBS-induced colitis. The protective effect is primarily mediated by probiotic DNA rather than live bacteria. Administration significantly attenuated clinical and histological severity. Protection is dependent on TLR9 signaling and MyD88 adaptor protein. In mice deficient in TLR9 or MyD88, the probiotic treatment failed to provide protection. DOI: 10.1053/j.gastro.2003.11.019

The De Simone Formulation was used as a reference to evaluate new probiotic combinations in protecting against chemically induced colitis. The research confirmed that the formulation provides significant protection by reducing pro-inflammatory gene expression and improving clinical outcomes. Treatment led to reduction in severity of weight loss and intestinal damage, confirming its established role in managing inflammatory bowel conditions. DOI: 10.3390/nu12071945

This clinical study evaluated the efficacy of the De Simone Formulation in treating diversion colitis in patients with an excluded colon segment. Patients were treated with rectal enemas containing the formulation twice daily for 15 days. Results showed significant improvement in both macroscopic and microscopic parameters, with notable reduction in inflammation, mucosal edema, and lymphoid follicles. The study concludes that local application is safe and effective. DOI: 10.3390/biology10040303

This study investigated combining the De Simone Formulation with Vitamin D3 in TNBS-induced colitis in rats. The formulation significantly reduced colitis severity, with lower damage scores and decreased neutrophil infiltration. The probiotic was particularly effective in preserving the mucosal barrier and modulating local immune response. While both showed individual benefits, the combination provided the most robust protection. DOI: 10.3390/nu17172719

In this open pilot study, 12 patients with acute diverticular colitis received oral beclomethasone dipropionate plus the De Simone Formulation. Eleven patients completed treatment; ten were completely asymptomatic at weeks 4 and 8, and one had only slight residual symptoms. Symptom, endoscopic, and histologic scores all improved significantly after therapy, with no significant adverse events reported. The authors propose that the topical steroid and formulation act synergistically through anti-inflammatory and microbiota-modulating mechanisms. J Clin Gastroenterol 39(7):644-645

This randomized pilot study evaluated maintenance strategies after remission of acute uncomplicated diverticulitis in 30 patients. Patients were randomized for 12 months to cyclic balsalazide plus De Simone Formulation, or De Simone Formulation alone. One relapse occurred in the combination group (6.7%) and two in the formulation-only group (13.3%). At 12 months, 73.3% of the combination group and 60% of the formulation-only group were completely symptom-free. Overall symptom scores were lower with combination therapy. No relevant side effects were observed. DOI: 10.1007/s00384-007-0299-6

This study assessed mucosal TNF-α expression in 10 patients with severe segmental colitis associated with diverticulosis before and after 8 weeks of treatment with beclomethasone dipropionate plus De Simone Formulation. TNF-α–positive stromal cells decreased significantly in both SCAD type B and D patients. In type B, all patients achieved clinical and endoscopic remission. In type D, clinical improvement occurred but without full remission. The findings indicate that SCAD shares an IBD-like TNF-α–driven inflammation and that response to treatment parallels TNF-α down-regulation. J Gastrointestin Liver Dis 20(4):365-370

In this pilot trial, 13 female patients with symptomatic uncomplicated diverticular disease received one of four 2-week regimens including the De Simone Formulation. Cumulatively, symptom scores significantly improved at all follow-up points. Metabolomic profiles showed marked shifts at days 14 and 44. Principal component analysis suggested that patients receiving De Simone Formulation experienced a more sustained, linear symptom improvement compared with other treatments, supporting a role for microbiota- and metabolome-targeted therapy in this condition. J Biol Regul Homeost Agents 32(6)

The study tested the De Simone Formulation in 224 children with acute rotavirus diarrhea. Compared with placebo, the probiotic led to earlier reduction in stool frequency, improved stool consistency, and lower oral rehydration solution use starting from Day 2. Benefits persisted through Day 4, with significantly higher recovery rates and no adverse events. The formulation shortened illness duration and reduced fluid losses. J Clin Gastroenterol. 2008;42(Suppl 3):S126–S129

Eighty dyspeptic adults with confirmed H. pylori infection received either the De Simone Formulation for 10 days or placebo. Thirteen of 40 treated patients became H. pylori–negative, while none in the placebo group cleared the infection. The probiotic markedly reduced urea breath test delta values, indicating decreased bacterial load. Subsequent standard triple therapy achieved similar eradication rates in both groups, showing that prior probiotic use did not impair antibiotic efficacy. Inflammation & Allergy – Drug Targets. 2012;11:244–249

This double-blind, placebo-controlled trial evaluated the efficacy of the De Simone Formulation in treating infantile colic in infants aged 0 to 4 months. The formulation was significantly more effective than placebo in reducing infant crying time. The percentage of "responders" (infants with at least a 50% reduction in crying time) was notably higher in the probiotic group. Analysis suggested efficacy is associated with positive changes in bacterial composition and intestinal metabolic activity. DOI: 10.3390/nu10111585

This review discusses the role of intestinal microflora in IBS pathogenesis and the therapeutic potential of oral bacteriotherapy. The authors highlight how alterations in gut microbiota may contribute to typical IBS symptoms. The paper emphasizes clinical evidence supporting the use of the De Simone Formulation, noting its ability to modulate the gut ecosystem, strengthen the intestinal barrier, and reduce low-grade inflammation. DOI: 10.1016/s1590-8658(02)80164-5

This study investigated sequential treatment in 106 infertile men with chronic bacterial prostatitis and IBS. Patients receiving rifaximin followed by De Simone Formulation for 12 months had significantly lower progression to complex infections compared to untreated group. The treated group showed significant improvements in ultrasound parameters and reduced inflammatory leukocytes in semen. The study concludes that the formulation improves intestinal barrier function and reduces bacterial migration. DOI: 10.4103/1008-682X.128509

This randomized, double-blind, placebo-controlled study explored whether the De Simone Formulation's mechanism involves melatonin regulation. Patients treated for six weeks experienced significant reduction in abdominal pain duration and bloating intensity. A positive correlation was observed between increased rectal distension pain tolerance and improved pain scores, suggesting probiotic-induced visceral desensitization. Salivary analysis showed increased melatonin levels in the probiotic group. DOI: 10.1007/s10620-014-3299-8

This landmark study evaluated the efficacy of the De Simone Formulation in maintaining remission in 40 patients with chronic pouchitis. After inducing remission with antibiotics, patients were randomized to receive either 6 g/day of the formulation or placebo for nine months. Results: 85% (17 of 20) of patients in the De Simone Formulation group remained in remission, compared to 0% (0 of 20) in the placebo group (P < 0.001). Fecal concentrations of beneficial bacteria increased significantly in the probiotic group. The study concluded that oral bacteriotherapy with the De Simone Formulation is an effective and safe maintenance treatment. DOI: 10.1053/gast.2000.9371

This research investigated the molecular mechanisms through which the De Simone Formulation exerts its anti-inflammatory effects in patients with pouchitis. Results showed that the formulation significantly reduced mucosal levels of pro-inflammatory cytokines (TNF-α and IL-1β), while increasing anti-inflammatory IL-10. Additionally, the probiotic led to significant downregulation of inducible nitric oxide synthase (iNOS) and matrix metalloproteinases (MMP-2 and MMP-9), which are key mediators of tissue damage. DOI: 10.1111/j.1572-0241.2001.04117.x

This trial aimed to determine if the De Simone Formulation could prevent the initial onset of acute pouchitis. Forty patients who underwent ileal pouch-anal anastomosis for ulcerative colitis were randomized to receive the formulation (900 billion bacteria/day) or placebo for one year, starting immediately after ileostomy closure. Only 10% (2 of 20) of patients treated with the formulation developed pouchitis during the first year, whereas 40% (8 of 20) of those in the placebo group experienced the condition (P < 0.05). Patients in the probiotic group reported significantly higher quality of life scores. DOI: 10.1053/gast.2003.50141

This study explored the effectiveness of once-daily high-dose administration of the De Simone Formulation in 36 patients with refractory or frequently relapsing pouchitis. After induction of remission with antibiotics, patients received 6 g of the formulation once daily or placebo for one year. At the end of the trial, 85% (17 of 20) of the probiotic-treated patients were still in remission, compared to only 6% (1 of 16) of the placebo group (P < 0.0001). Quality of life remained stable in the probiotic group but deteriorated significantly in the placebo group. DOI: 10.1136/gut.53.1.108

This study used molecular techniques to analyze how the De Simone Formulation modulates the microbial community of the ileal pouch. The formulation significantly increased total bacterial diversity and the specific concentrations of the probiotic strains. Interestingly, it also impacted the fungal community, leading to a reduction in the diversity of fungal species in the pouch mucosa. Clinically, the shift towards a more diverse bacterial flora and a simplified fungal flora was associated with the maintenance of remission. DOI: 10.1136/gut.2005.078303

Unlike previous trials focused on prevention or maintenance, this study evaluated the De Simone Formulation as a primary treatment for mildly active pouchitis. Twenty-three patients with a PDAI score between 7 and 12 were treated with a very high dose (3,600 billion bacteria/day) for four weeks. Remission was achieved in 69% (16 of 23) of patients, with a significant decrease in the mean PDAI score from 10.1 to 4.8. No significant side effects were reported despite the high dosage. DOI: 10.1007/s10350-007-0241-1

This open-label study investigated the immunological impact of the De Simone Formulation in 31 asymptomatic patients who had undergone ileal pouch-anal anastomosis. Patients were randomized to receive the formulation or no treatment for 12 months. Probiotic administration was associated with a significant expansion of mucosal regulatory T cells (CD4+CD25high) in the pouch, increased expression of Foxp3, and reduced pro-inflammatory markers like IL-1β and IL-8. These immunological changes were observed even in patients who began treatment long after surgery. DOI: 10.1002/ibd.20369

This preliminary open-label study evaluated the effects of the De Simone Formulation on fecal flora and clinical efficacy as maintenance therapy in 20 patients with ulcerative colitis in remission who were intolerant to 5-ASA. Patients were treated for 12 months. Microbiological analysis demonstrated that fecal concentrations of Bifidobacteria, Lactobacilli, and Streptococcus increased significantly. Clinically, 15 out of 20 patients (75%) remained in remission for the entire duration of the study. DOI: 10.1046/j.1365-2036.1999.00534.x

This open-label study involved thirty-four patients with mild-to-moderate active ulcerative colitis who were non-responsive to conventional therapy, evaluating the efficacy of the De Simone Formulation (3,600 billion bacteria per day) for six weeks. Intent-to-treat analysis demonstrated 53% of patients achieving remission (UCDAI ≤ 2) and an additional 24% showing a clinical response, resulting in a combined success rate of 77%. Treatment was safe and well-tolerated, with mild bloating as the only adverse event. At least two bacterial species from the product reached the disease site. DOI: 10.1111/j.1572-0241.2005.41794.x

This open-label pilot study evaluated the efficacy of the De Simone Formulation in 18 children with mild-to-moderate acute ulcerative colitis. Patients received the formulation daily for eight weeks in addition to standard therapy. Results showed that 56% of children achieved clinical remission (PUCAI score < 10), and an additional 6% showed a significant clinical response. Endoscopic and histological scores also improved significantly (p < 0.05). The formulation was well-tolerated by the pediatric population. DOI: 10.1002/ibd.20816

This double-blind, randomized, placebo-controlled study investigated the efficacy of the De Simone Formulation as add-on therapy to standard treatment (5-ASA and/or steroids) in 144 patients with relapsing mild-to-moderate ulcerative colitis. The primary endpoint was achieved in 63.1% of patients in the formulation group compared to 40.8% in placebo (p = 0.01). The remission rate was significantly higher (42.2% vs. 15.7%, p = 0.0003). Clinical response rates were also significantly improved (59.4% vs. 23.6%, p < 0.0001). The study concluded that using the formulation as adjunctive therapy is safe and highly effective. DOI: 10.1038/ajg.2010.218

Maternal supplementation with the De Simone Formulation from the 36th week of pregnancy to the first month postpartum significantly altered the cytokine profile of breast milk. Treated mothers showed higher levels of IL-10 and TGF-β1 and a reduction in IL-6 in the transition from colostrum to mature milk. In newborns, stools showed higher concentrations of sIgA, suggesting enhanced mucosal immunity. Clinically, newborns in the probiotic group showed a lower incidence of colic and regurgitation. DOI: 10.3390/nu8110677

Maternal supplementation with De Simone Formulation significantly increased concentrations of lactobacilli and bifidobacteria in breast milk, but only in women who delivered vaginally. None of the probiotic strains were detected in the milk, suggesting an indirect effect rather than bacterial transfer. No changes in oligosaccharide or lactoferrin levels were observed. The effect was absent in women who underwent cesarean section, likely due to intrapartum antibiotic use. DOI: 10.1016/j.phrs.2015.03.013

Oral administration of the De Simone Formulation in the final weeks of pregnancy modulated the composition of the vaginal microbiota, evidenced by changes in DGGE profiles. The supplementation counteracted the physiological decrease in bifidobacteria and the increase in Atopobium observed in the control group. At the immune level, the probiotic group showed a reduction in eotaxin and maintained stable levels of IL-4 and IL-10, which decreased in the control group, suggesting a potential vaginal anti-inflammatory effect. DOI: 10.1186/1471-2180-12-236

In mouse models, estrogen deprivation induces bone loss through increased intestinal permeability, expansion of Th17 cells, and increased levels of TNF, RANKL, and IL-17. In germ-free mice, these effects do not occur, demonstrating dependence on the microbiota. Administration of the De Simone Formulation completely prevented bone loss, reduced intestinal permeability, and normalized cytokine levels. The effect was not observed with non-probiotic or mutant strains. DOI: 10.1172/JCI86062

In obese pregnant women, the De Simone Formulation taken from the second trimester until delivery did not affect gestational weight, blood glucose, or the incidence of GDM. However, it significantly increased the alpha diversity of the gut microbiota over time, an effect not observed in the placebo group. No impact on neonatal outcomes was observed. DOI: 10.1093/cdn/nzaa095

In women with asymptomatic BV, two months of oral administration of the De Simone Formulation significantly reduced the richness and diversity of the vaginal microbiota, decreasing genera associated with dysbiosis (e.g., Megasphaera) and doubling the relative abundance of lactobacilli. No changes were observed in healthy women. The results suggest a rebalancing toward a more eubiotic vaginal ecosystem. DOI: 10.3390/nu16203469

This study investigated whether a synbiotic regimen comprising the De Simone Formulation and prebiotics could enhance gastrointestinal immunity in SIV-infected pigtail macaques receiving antiretroviral therapy. The combination treatment significantly increased the frequency and absolute number of Th17 and Th22 cells within the GI tract compared to ART alone. Furthermore, the formulation led to reduced levels of immune activation and improved GI tract structure and function. DOI: 10.1172/JCI66227

This research examined the impact of the De Simone Formulation on the immune system of healthy pigtail macaques. Following oral administration, there was a notable increase in the frequency of Th17 and Th22 cells in the colonic mucosa, along with an enhancement in the proportion of IL-10-producing antigen-presenting cells. The study also observed a decrease in systemic T-cell activation and a reduction in signaling through several Toll-like receptors in vitro. DOI: 10.4049/jimmunol.1502470

In SIV-infected macaques treated with antiretrovirals, combined therapy with IL-21 and the De Simone Formulation significantly increased the frequencies of Th17 cells in the jejunum and rectal biopsies. The formulation was associated with a decrease in microbial translocation (lower plasma sCD14 levels) and a reduction in the kynurenine/tryptophan ratio. The treatment also successfully modulated the gut microbiome, increasing Lactobacillus and Bifidobacterium abundance. DOI: 10.1038/mi.2015.75

This pilot study investigated the effects of the De Simone Formulation on immune activation markers in HIV-1 infected patients receiving ART. After 6 months of supplementation, results showed a significant reduction in IDO1 mRNA expression in the GALT and a decrease in CSF neopterin levels. These changes suggest that the formulation may help mitigate systemic and central nervous system inflammation by modulating the kynurenine pathway and reducing macrophage activation. DOI: 10.3390/ijms17101639

This pilot trial explored the potential of high-dose De Simone Formulation to improve neurocognitive function in HIV-positive patients on stable ART. After six months of supplementation, patients showed a significant improvement in several neuropsychological tests, particularly those assessing executive functions and processing speed. The study monitored levels of the miR-29 family, though no significant changes were observed in these specific microRNAs during the study period. DOI: 10.1002/brb3.756

This study investigated the effects of the De Simone Formulation on CNS inflammation and cognitive performance in ART-treated HIV patients. Participants receiving the formulation for six months demonstrated significant improvements in neurocognitive scores compared to baseline. Furthermore, the study reported a significant reduction in several biomarkers of CNS immune activation and inflammation in the cerebrospinal fluid, such as neopterin. These results support the hypothesis that the formulation can modulate the gut-brain axis. DOI: 10.3390/nu9111269

This study analyzed the impact of the De Simone Formulation on gut-associated lymphoid tissue and systemic immunity in HIV-infected individuals. After six months of high-dose supplementation, researchers observed a significant decrease in activation markers (CD38 and HLA-DR) on both CD4+ and CD8+ T cells in the GALT. There was also a notable increase in the frequency of Th17 cells and restoration of the Th17/Treg ratio. Morphological analysis revealed that the formulation helped recover the integrity of the epithelial barrier and improved mitochondrial structure within enterocytes. DOI: 10.1002/iid3.162

This study examined how the De Simone Formulation affects the metabolism of tryptophan in HIV-positive individuals on stable ART. Following probiotic supplementation, researchers observed a significant decrease in the kynurenine/tryptophan ratio and a corresponding increase in serotonin levels in the plasma. Furthermore, the expression of IDO1 in the gastrointestinal mucosa was significantly downregulated. These findings indicate that the formulation can effectively redirect tryptophan metabolism toward beneficial pathways. DOI: 10.1177/1178646917710668

This research compared the original De Simone Formulation with a newer version marketed under the same brand name but produced at a different manufacturing site. The study used various in vitro models to assess biological activity, including the ability to induce anti-inflammatory cytokines, protect epithelial barrier integrity, and inhibit pathogen internalization. The results demonstrated significant differences in performance, with the original De Simone Formulation showing superior efficacy. The authors conclude that the specific manufacturing process is critical to the biological profile and clinical safety. DOI: 10.3389/fimmu.2017.01474

This case report describes a 56-year-old HIV-infected man with persistent anal condylomas and HPV-18 infection who was treated with the De Simone Formulation. The patient received the formulation both orally and via endorectal instillation for four months to enhance local mucosal immunity. At the end of treatment, a pelvic MRI confirmed complete clearance of the anal condylomas and resolution of previously observed reactive lymphadenopathies. The authors suggest that the formulation may boost local immune responses against HPV. DOI: 10.1097/MD.0000000000013357

This investigation aimed to determine if the De Simone Formulation could induce direct antiviral effects within the gut of HIV-infected patients. Fecal water samples were collected from patients before and after six months of supplementation. The study found that fecal water from the post-supplementation period significantly inhibited HIV-1 replication in vitro when compared to baseline samples. Additionally, treatment was associated with a reduction in systemic T-cell activation markers. The results suggest that the formulation promotes an intestinal environment that is less permissive to viral activity. DOI: 10.2174/1570162X17666190903230622

This study utilized a proteomic approach to examine changes in the cerebrospinal fluid of HIV patients following supplementation with the De Simone Formulation. After six months of therapy, patients showed significant improvements in neurocognitive performance across several domains. Proteomic analysis of the CSF identified differential expression of proteins involved in inflammatory responses, oxidative stress, and lipid metabolism. Specifically, the formulation appeared to modulate pathways related to protease inhibition and vascular integrity. These molecular changes provide a potential mechanistic explanation for the observed improvements in cognitive function. DOI: 10.1007/s13365-019-00801-7

This clinical trial evaluated the efficacy of the De Simone Formulation in treating anal HPV infection and associated dysplasia in HIV-positive men who have sex with men. Participants were randomized to receive either the formulation or no probiotic for six months. The group receiving the formulation showed a significantly higher rate of clearance for high-risk HPV strains and a higher percentage of regression from low-grade squamous intraepithelial lesions compared to the control group. These clinical improvements were accompanied by a decrease in local inflammatory markers. DOI: 10.3390/biomedicines9111738

This study investigated whether the De Simone Formulation could enhance the vaccine-induced immune response in HIV-positive patients. Participants were randomized to receive the 13-valent pneumococcal conjugate vaccine alone or in combination with the formulation. After 4 weeks, the group receiving the probiotic showed significantly higher levels of specific IgG antibodies against pneumococcal polysaccharides compared to the control group. Additionally, the probiotic group exhibited a more favorable cytokine profile, with increased production of IL-10 and IFN-gamma. The results suggest that the formulation acts as an effective adjuvant. DOI: 10.3390/nu13124412

The PROCOG study was a randomized, double-blind, placebo-controlled trial designed to assess the impact of the De Simone Formulation on neurocognitive performance and immune activation in HIV-positive patients. Patients with stable ART and mild-to-moderate neurocognitive impairment received either high-dose formulation or placebo for 6 months. Results indicated a significant improvement in global neurocognitive scores in the probiotic group, particularly in the domains of memory and executive function. This clinical improvement was accompanied by a reduction in plasma markers of monocyte activation (sCD14). DOI: 10.3390/pathogens14010042

This study evaluated the effect of 4-week daily consumption of the De Simone Formulation on gastrointestinal oxalate absorption in 11 healthy volunteers. Mean total 22-hour oxalate absorption significantly decreased from 30.8% at baseline to 11.6% after treatment. This reduction was particularly pronounced in high oxalate absorbers. Decreased absorption levels persisted even after the 4-week washout period. The study concludes that the formulation has potential to lower the risk of calcium oxalate stone formation. DOI: 10.1007/s00240-010-0262-9

This research investigated whether simultaneous acute ingestion of the De Simone Formulation with an oxalate-rich load could reduce oxalate absorption. Eleven healthy subjects were administered a 176 mg oxalate load either alone or alongside a single or double dose of the formulation. Both doses were effective in significantly reducing urinary oxalate excretion and estimated oxalate absorption compared to control. No significant difference was found between the two probiotic doses. The timing suggests that the formulation acts early in the digestive process. DOI: 10.1007/s00240-011-0421-7

This study evaluated the efficacy of the De Simone Formulation in modulating intestinal permeability and immune function in 28 critically ill patients. Participants were randomized to receive placebo, viable De Simone Formulation, or probiotic sonicates for 7 days. Results showed that patients receiving the viable formulation had a significantly greater increase in systemic IgA and IgG concentrations compared to those receiving the placebo or sonicates. However, no significant differences were observed in intestinal permeability or MODS scores among the groups. DOI: 10.1093/ajcn/85.3.816

This research investigated the impact of the De Simone Formulation on intestinal barrier function and hepatic injury in a mouse model of sepsis induced by LPS/GalN. Mice treated with the formulation for 7 days showed significantly reduced bacterial translocation to the liver and lower levels of pro-inflammatory cytokines (TNF-α and IL-6). The study also demonstrated that the formulation maintained colonic barrier integrity and reduced epithelial permeability. These protective effects were partially mediated by the induction of PPARγ. DOI: 10.1002/hep.21757

This pilot trial explored the efficacy of the De Simone Formulation in reducing diarrhea among 45 enterally fed critically ill patients. Patients received either the formulation or placebo twice daily for the duration of their enteral nutrition. The study found that the group receiving the formulation had a significant reduction in the mean number of episodes of liquid stool compared to the control group. There were no adverse effects related to the probiotic administration. DOI: 10.4037/ajcc2010976

This study assessed whether the De Simone Formulation could protect against small bowel damage caused by NSAIDs. Twenty healthy volunteers received indomethacin combined with either the formulation or placebo in a cross-over design. Intestinal damage was measured using fecal calprotectin concentrations (FCC). Results indicated that while indomethacin significantly increased FCC in both groups, the increase was significantly lower when participants were taking the formulation. This suggests that the formulation may mitigate the intestinal inflammation and enteropathy typically associated with NSAID use. DOI: 10.1111/j.1365-2036.2010.04324.x

The PROAGE study evaluated the impact of the De Simone Formulation on bowel movements and infections in 243 hospitalized elderly patients. Participants were randomized to receive the formulation or placebo for 21 days. The results showed that the group treated with the formulation had a significant increase in the number of days with normal bowel movements and a decrease in the incidence of constipation compared to the placebo group. No significant differences were found in the incidence of infections. DOI: 10.1007/s12603-010-0124-x

Using a computer-controlled in vitro model of the large intestine, this research examined the interaction between the antibiotic clindamycin and the De Simone Formulation. The study found that clindamycin significantly disrupted the microbial community and reduced the production of beneficial short-chain fatty acids. The addition of the formulation helped to stabilize the metabolic activity of the microbiota, increasing the production of lactate and certain SCFAs. These findings suggest that the formulation can help maintain or restore intestinal homeostasis during antibiotic treatment. DOI: 10.1186/1471-2180-12-47

This pilot study investigated the effects of the De Simone Formulation on inflammation and oxidative stress in 40 critically ill patients. Patients were randomized to receive the formulation or placebo for 7 days. The results showed a significant reduction in C-reactive protein (CRP) levels and APACHE II scores in the group receiving the formulation compared to the placebo group. No significant changes were observed in total antioxidant capacity or malondialdehyde levels. DOI: 10.12669/pjms.292.3134

This trial examined the impact of the De Simone Formulation on lipid profiles and cardiovascular risk in 40 critically ill patients. Participants received either the probiotic formulation or placebo for 7 days. The group treated with the formulation showed a significant decrease in serum total cholesterol, LDL-cholesterol, and VLDL-cholesterol levels compared to baseline and the control group. No significant changes were seen in HDL-cholesterol or triglyceride levels. DOI: 10.5681/jcvtr.2013.014

This study evaluated whether the early postoperative administration of the De Simone Formulation could improve recovery in 60 elderly patients undergoing colorectal surgery. Patients were randomized to receive the formulation or placebo starting on the first postoperative day. The probiotic group showed a significantly earlier return of bowel function (first flatus and first bowel movement) and a shorter hospital stay compared to the placebo group. Additionally, the incidence of postoperative complications was lower in the treatment arm. DOI: 10.1186/1471-2482-13-S2-S57

This randomized controlled trial investigated the ability of the De Simone Formulation to prevent antibiotic-associated diarrhea (AAD) in 229 hospitalized patients. Participants receiving systemic antibiotics were randomized to receive the formulation or placebo for the duration of their antibiotic course plus 7 days. The study found that the incidence of AAD was significantly lower in the formulation group compared to the placebo group. Furthermore, no cases of Clostridium difficile-associated diarrhea were reported in the probiotic group. DOI: 10.1016/j.jhin.2013.02.019

This randomized controlled trial evaluated the effect of the De Simone Formulation on systemic inflammation in 40 critically ill patients in the ICU. Patients received either the probiotic formulation or placebo for 7 days. The research demonstrated that the formulation significantly reduced the levels of pro-inflammatory cytokines, specifically Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α), compared to the placebo group. Additionally, the probiotic group showed a significant improvement in clinical severity as measured by the APACHE II score. Journal of Research in Medical Sciences 2014;19:1069-73

This pilot study assessed the safety and tolerability of the De Simone Formulation in 30 patients colonized with Vancomycin-Resistant Enterococcus (VRE). Participants were randomized to receive the probiotic or placebo for 21 days. The primary focus was on the frequency of gastrointestinal adverse events and the impact on VRE colonization levels. The results indicated that the formulation was well-tolerated, with no significant differences in adverse events between the two groups. While there was no significant reduction in VRE colonization density compared to placebo, the study confirmed that high-dose probiotic administration is safe even in patients carrying multi-drug resistant organisms. DOI: 10.4172/2329-8901.1000142

This study investigated the effectiveness of the De Simone Formulation and lactulose in preventing the recurrence of overt hepatic encephalopathy in cirrhotic patients. In this open-label trial, 235 patients were randomized to receive lactulose, the formulation, or no treatment. Over a 12-month follow-up, both the probiotic group and the lactulose group showed significantly lower rates of HE recurrence compared to the control group. Specifically, HE developed in 19.7% of patients in the probiotic group and 13.8% in the lactulose group, versus 46.8% in the no-therapy group. DOI: 10.1038/ajg.2012.113

This randomized, double-blind, placebo-controlled trial evaluated whether adding the De Simone Formulation to propranolol could further reduce the hepatic venous pressure gradient (HVPG) in cirrhotic patients with large varices. Patients received either the probiotic or placebo alongside propranolol for two months. While propranolol effectively reduced HVPG in both groups, the addition of the formulation did not lead to a significantly greater reduction compared to placebo. However, the study noted that the formulation might influence the response rate to beta-blockers. DOI: 10.1111/liv.12172

This double-blind RCT assessed the efficacy of the De Simone Formulation in obese children with biopsy-proven non-alcoholic steatohepatitis (NASH). Forty-four children were randomized to receive the probiotic or placebo for four months. The primary outcome was the improvement of fatty liver severity measured by ultrasonography. The group treated with the formulation showed a significantly higher rate of improvement in liver steatosis compared to the placebo group. Additionally, a significant reduction in Body Mass Index (BMI) was observed in the probiotic group. DOI: 10.1111/apt.12758

This trial investigated whether the De Simone Formulation could prevent breakthrough hepatic encephalopathy and reduce hospitalizations in cirrhotic patients. In a 6-month double-blind study, 130 patients were randomized to receive the probiotic or placebo. The formulation significantly reduced the risk of hospitalization and improved liver disease severity as measured by MELD and Child-Pugh scores. Although there was a trend toward reduced HE recurrence, the most significant impact was seen in the reduction of overall complications and hospital stays. DOI: 10.1053/j.gastro.2014.08.031

This study explored the use of the De Simone Formulation for the primary prophylaxis of hepatic encephalopathy in cirrhotic patients without a history of overt HE. One hundred sixty patients were randomized to receive the probiotic or no treatment. Over an average follow-up of 10 months, significantly fewer patients in the formulation group developed overt HE (1.1%) compared to the control group (18.9%). The probiotic also improved psychometric test scores and reduced arterial ammonia levels. DOI: 10.1016/j.cgh.2013.11.033

This study aimed to determine if the De Simone Formulation could improve systemic haemodynamics in patients with cirrhosis and ascites. In a pilot trial, 12 patients received the probiotic for six weeks. Treatment with the formulation led to a significant increase in systemic vascular resistance and a decrease in cardiac output, effectively attenuating the hyperdynamic circulatory state typical of advanced cirrhosis. These changes were accompanied by a reduction in plasma levels of renin and aldosterone. DOI: 10.1111/liv.12539

This research utilized metabolic profiling to identify non-invasive biomarkers of response to the De Simone Formulation in children with non-alcoholic fatty liver disease. Using urine samples from a previous trial, the authors found that probiotic treatment induced significant changes in host metabolic phenotypes. Specifically, the formulation affected amino acid metabolism and gut microbiota-derived metabolites. These metabolic shifts correlated with the clinical improvement in liver steatosis and BMI. The study demonstrates that urinary metabolomics can provide insights into the mechanisms by which the formulation exerts its beneficial effects on liver health. DOI: 10.1038/ijo.2015.41

This study compared the efficacy of the De Simone Formulation to the standard treatment, lactulose, for minimal hepatic encephalopathy. In a randomized non-inferiority trial, 120 patients received either the probiotic or lactulose for two months. The formulation was found to be non-inferior to lactulose, with 54% of patients in the probiotic group and 47% in the lactulose group showing normalization of psychometric and neurophysiological tests. The study concludes that the formulation is a viable and well-tolerated alternative to lactulose. DOI: 10.1111/hepr.12429

This proof-of-concept study evaluated the effect of the De Simone Formulation on liver histology in patients with NAFLD. Thirty patients were randomized to receive the probiotic or placebo for one year. Liver biopsies performed before and after treatment showed that the formulation group had a significant improvement in the NAFLD Activity Score (NAS), which measures steatosis, inflammation, and ballooning. No such improvement was seen in the placebo group. The results suggest that long-term use of the formulation can lead to histological improvement in liver damage caused by NAFLD. DOI: 10.1136/bmjgast-2019-000315

This randomized, double-blind, placebo-controlled trial evaluated the impact of the De Simone Formulation on cognitive function and the risk of falls in 36 outpatients with cirrhosis. Patients received either two sachets daily of the formulation (450 billion bacteria per sachet) or placebo for 12 weeks. The results demonstrated that the formulation significantly improved cognitive function (P=0.006) and reduced the risk of falling, evidenced by improved test times (P=0.015) and increased gait speed (P=0.02). The study also observed a decrease in systemic inflammatory markers (CRP and TNF-α) and improved intestinal barrier integrity. No adverse events were attributed to the product. DOI: 10.1002/hep4.1325

This pilot study examined the impact of the De Simone Formulation on portal pressure, measured by HVPG, in patients with decompensated cirrhosis. In a randomized, double-blind, placebo-controlled crossover design, patients received the probiotic for six weeks. The results indicated that the formulation did not significantly reduce HVPG, nor did it significantly alter systemic haemodynamics or levels of inflammatory markers like TNF-alpha or IL-6. The study concluded that while safe, the formulation did not show a clinical benefit in reducing portal hypertension in this specific patient population with advanced liver disease. DOI: 10.1111/liv.12280

This study investigated the impact of the De Simone Formulation on the gut microbiome and peripheral immune function in healthy individuals and patients with relapsing-remitting multiple sclerosis. Results showed that oral administration of the probiotic twice daily for two months significantly increased the abundance of taxa typically depleted in MS, such as Lactobacillus, while decreasing taxa associated with dysbiosis, including Akkermansia and Blautia. At the immune level, the formulation induced an anti-inflammatory response characterized by a reduction in the frequency of inflammatory monocytes and decreased expression of activation markers (CD80, HLA-DR) on classical monocytes and dendritic cells. DOI: 10.1002/ana.25244

In this pilot study, researchers evaluated the effects of the De Simone Formulation on the gut microbiota and peripheral immune system of healthy controls and MS patients. Administration of the probiotic was linked to a significant increase in the abundance of beneficial bacterial taxa, predominantly Lactobacillus, Streptococcus, and Bifidobacterium species. Immunologically, the formulation promoted an anti-inflammatory environment by decreasing the frequency of intermediate monocytes and reducing the mean fluorescence intensity (MFI) of the co-stimulatory molecule CD80 on classical monocytes. Additionally, a reduction in HLA-DR MFI on dendritic cells was observed. DOI: 10.1177/1352458517737390

This Phase II trial assessed whether the De Simone Formulation could improve gastrointestinal symptoms in patients with systemic sclerosis. Patients were randomized to receive a high dose of the formulation (1800 billion units/day) or placebo for 60 days, followed by an additional 60 days where both groups received the probiotic. While no significant improvement in total GI scores was found after the first 60 days, a significant improvement in GI reflux was observed in the probiotic group after 120 days of treatment (p=0.004). The study also noted an increase in stool microbiota alpha diversity among subjects taking the probiotic. DOI: 10.1016/j.semarthrit.2019.05.006

This study utilized a murine model of primary progressive multiple sclerosis to investigate the effects of the De Simone Formulation on neurodegeneration and immune responses. Administration of the formulation significantly improved motor disability in infected mice. In the CNS, the probiotic reduced microgliosis, astrogliosis, and leukocyte infiltration while enhancing the presence of regulatory B cells. One of the most significant findings was a notable increase in plasma levels of the short-chain fatty acids butyrate and acetate. Furthermore, the probiotic restricted the production of the pro-inflammatory cytokine IL-17 by Th17 cells and promoted IL-10 expression in the spinal cord. DOI: 10.1080/19490976.2020.1813532

This case report details the treatment of a 52-year-old male suffering from obesity, metabolic syndrome, and severe gastroesophageal reflux disease. The patient presented with elevated plasma lipopolysaccharide levels, suggesting dysbiosis and metabolic endotoxemia. Following a three-month intervention with the De Simone Formulation, the patient experienced a significant reduction in digestive symptoms, including the resolution of morning nausea and abdominal bloating. Furthermore, there were notable improvements in anthropometric and cardiometabolic parameters: the patient lost 5 kg, reduced his waist circumference by 7 cm, and showed improved lipid and glycemic profiles. Blood pressure also normalized during the treatment. Advances in Obesity, Weight Management & Control, 2(4), 00028

This document outlines the protocol for a randomized, double-blind, placebo-controlled trial designed to investigate whether the De Simone Formulation can limit gestational weight gain and improve metabolic health in obese pregnant women. The study planned to enroll 120 women with a BMI between 30 and 45 kg/m², randomizing them to receive either the formulation or placebo from the second trimester until delivery. The primary outcome measure was the difference in gestational weight gain. Secondary outcomes included maternal glucose metabolism, inflammatory markers, and the composition of the gut microbiota in both mothers and their newborns. DOI: 10.1186/s13063-016-1617-5

This pilot study assessed the impact of the De Simone Formulation on gut microbiota and insulin resistance in 15 adolescents with severe obesity. Participants received either the probiotic or placebo for 12 weeks. While weight and BMI did not show significant changes between groups, the group receiving the formulation exhibited a significantly lower increase in fasting glucose compared to the placebo group (P=0.028). Additionally, the probiotic group showed a more pronounced decline in the Firmicutes-to-Bacteroidetes ratio, a marker often associated with obesity-related dysbiosis. The study also observed changes in specific bacterial abundances, such as an increase in Akkermansia and a decrease in Eubacterium. DOI: 10.1007/s40200-021-00855-7

This study reported the clinical results of the trial previously described in the 2016 protocol. 110 obese pregnant women completed the intervention, receiving either the De Simone Formulation or placebo. The results indicated that the formulation did not significantly affect gestational weight gain, fasting glucose, insulin levels, or HOMA-IR compared to placebo. Similarly, there were no significant differences in systemic inflammatory markers (hs-CRP, IL-6, TNF-α) or newborn body composition (birth weight, fat mass). Both groups showed a similar increase in several inflammatory markers during pregnancy. The study concludes that while the formulation is safe and well-tolerated during pregnancy, it does not appear to provide significant metabolic or anti-inflammatory benefits in this specific population. DOI: 10.1016/j.nmcd.2023.07.020

This analysis focused on the secondary outcomes of the trial involving obese pregnant women, specifically examining the development of the infant gut microbiome. Stool samples from infants were analyzed at birth and at nine months of age. The results showed that infants born to mothers who took the De Simone Formulation during pregnancy had a significantly higher alpha diversity (Shannon index) and a different microbial composition (beta diversity) at nine months compared to the placebo group. Specifically, these infants exhibited a higher abundance of beneficial bacteria, such as Akkermansia, and a lower abundance of Collinsella. These findings suggest that maternal intake of the formulation during pregnancy can have long-term effects on the infant's gut microbiome development. DOI: 10.1080/19490976.2024.2337968

This double-blind, placebo-controlled randomized trial investigated the efficacy of the De Simone Formulation in preventing radiation-induced diarrhea in 490 patients undergoing adjuvant postoperative radiation therapy for sigmoid, rectal, or pelvic cancer. Participants received either the formulation (one sachet three times daily) or placebo. Results showed that significantly fewer patients in the formulation group experienced radiation-induced diarrhea compared to the placebo group (31.6% vs. 51.8%, P < 0.001). Furthermore, the severity of diarrhea was lower in the probiotic group, with fewer patients experiencing grade 3 or 4 diarrhea. The study also reported a significant reduction in the mean number of daily bowel movements and a decreased requirement for loperamide rescue medication. DOI: 10.3748/wjg.v13.i6.912

This study utilized a rat model to evaluate the potential of the De Simone Formulation to mitigate gastrointestinal toxicity caused by the chemotherapy drug irinotecan. Female Dark Agouti rats were administered the formulation via oral gavage for seven days prior to a single dose of irinotecan. Results demonstrated that the formulation significantly reduced the incidence and severity of chemotherapy-induced diarrhea, particularly at the 6-hour and 72-96 hour marks post-treatment. Additionally, rats treated with the formulation experienced significantly less weight loss compared to the irinotecan-only group. Histological analysis showed that the probiotic treatment helped maintain the integrity of the intestinal crypts and reduced the severity of mucosal damage. DOI: 10.4161/cbt.6.9.4622

This case study reports on a 50-year-old female patient with stage IV breast cancer who developed severe grade 3 diarrhea while undergoing chemotherapy with capecitabine and lapatinib. After failing standard anti-diarrheal treatments, the patient was prescribed the De Simone Formulation (one sachet twice daily). Within three days of starting the probiotic treatment, the patient's bowel movements reduced from 7-9 per day to just one, and the associated abdominal cramping and incontinence resolved completely. The patient was able to continue her chemotherapy regimen without further dose reductions or interruptions. DOI: 10.1177/0148607109332004

This research investigated the neuroprotective effects of the De Simone Formulation against chemotherapy-induced peripheral neuropathy using both in vitro and in vivo models. In mice treated with the chemotherapeutic agent paclitaxel, oral administration of the formulation significantly prevented the development of mechanical allodynia and thermal hyperalgesia. The probiotic treatment was found to downregulate pro-inflammatory cytokines, specifically IL-8 (CXCL8), and modulate the activation of the TLR4/NFκB signaling pathway in the peripheral nervous system. Furthermore, the formulation protected against mitochondrial dysfunction and axonal damage induced by chemotherapy. The study suggests that the formulation acts through the gut-brain-axis to reduce systemic and localized inflammation. DOI: 10.18632/oncotarget.25556

This study investigated sequential treatment in 106 infertile men with chronic bacterial prostatitis and IBS. Patients receiving rifaximin followed by De Simone Formulation for 12 months had significantly lower progression to complex infections (PV and PVE) compared to untreated group (P < 0.05). The treated group showed significant improvements in ultrasound parameters and reduced inflammatory leukocytes in semen. The study concludes that the formulation improves intestinal barrier function and reduces bacterial migration from the gut to the urogenital tract. DOI: 10.4103/1008-682X.128509